Generation of frequency-chirped optical pulses in a large-slippagefree-electron laser

We have investigated the optical output of the free-electron laser for infrared experiments (FELIX) when it is driven by an electron beam with a ramped energy. We show that the applied slow ramp on the electron beam energy leads to a frequency chirp on each picosecond optical pulse. Typical values for the chirp are 0.2% frequency sweep across a 1.5-ps-long optical pulse. The optical pulses were analyzed with a double-grating pair and with a second-order autocorrelator. The pulse duration was reduced in the double-grating pair by 20%. A linear dependence of the chirp on the cavity desynchronization was measured     

Interferon-gamma activates the oxidative killing of Candida albicans by human granulocytes

The sequence proline-proline-glycine-proline is highly conserved in cytochrome P450 families 1 and 2, and similar proline rich sequences are found in other cytochromes P450. Since this sequence immediately follows the NH2-terminal hydrophobic membrane insertion signal, it potentially could function as a signal either for retention of cytochrome P450 in the endoplasmic reticulum or for its correct orientation in the membrane. To test this possibility, DNA sequence coding for this tetrapeptide was deleted from cytochrome P450 2C2 cDNA. Translation of the mutated mRNA in a reticulocyte cell-free system containing canine microsomal membranes resulted in the insertion of the protein into the membrane with a topology indistinguishable from that of normal cytochrome P450 2C2. The mutated protein was expressed in COS1 cells and its distribution, assayed by immunofluorescence, was similar to that of cytochrome P450 2C2. Furthermore, if a short peptide containing a potential glycosylation site was fused to the N-terminus of the mutant protein, the new hybrid protein was glycosylated in COS1 cells and the carbohydrate moiety remained sensitive to cleavage by endoglycosidase H. These results indicate that the protein was inserted and retained in the endoplasmic reticulum membrane. Pulse-chase studies showed that the mutated protein was degraded about four times as fast as cytochrome P450 2C2. In contrast to cytochrome P450 2C2, no (omega-1) hydroxylase activity was detected in COS1 cells expressing the mutated protein at similar steady-state levels as the wild-type protein. These results indicate that, although the conserved PPGP tetrapeptide is not required for cellular localization of cytochrome P450 in the endoplasmic reticulum membrane, its deletion decreases the stability of the protein and abolishes enzymatic activity.     

Hypomagnesemia following correction of metabolic acidosis: a case of hungry bones

Severe symptomatic hypomagnesemia (0.15 mmol/L [0.3 mEq/L]) and hypocalcemia (1.47 mmol/L [5.9 mg/dL]) occurred in a 4-week-old infant coincidental with correction of a severe renal tubular acidosis with alkali therapy. The patient had no evidence of gastrointestinal abnormality and magnesium (Mg) intake was adequate for age and weight. Extreme renal conservation of Mg was observed, supporting the presence of Mg depletion. We suggest that Mg depletion in this infant occurred due to acidosis-induced bone demineralization and that symptomatic hypomagnesemia was precipitated by rapid remineralization accompanying correction of systemic acidosis. This patient represents a novel case of hungry bone syndrome (HBS). Since HBS has not been described previously in patients with acidosis undergoing therapy, several other factors may have contributed to this patient's severe hypomagnesemia, namely, prematurity, twin status, severity of acidosis, rapidity of correction of acidosis, catch-up growth and calcium supplementation. Clinicians should be vigilant for HBS in infants with severe acidosis undergoing alkali therapy.     

A little less sodium is not without hazard

Surgical thrombectomy is not a rational approach to neonatal renal vein thrombosis since the occlusion mainly involves intrarenal branches rather than the main renal vein, which is even patent in some instances. Conservative management combines supportive therapy for renal failure and systemic hypertension, if needed, and either heparin or thrombolytic agents. Streptokinase has proven difficult to handle in neonates and should not be used. Urokinase has been used in 18 patients but results are difficult to interpret because these cases occurred over an 18-year period. Plasminogen tissue activator, the latest thrombolytic agent developed, has been used in few pediatric patients. An international task force is currently studying whether or not a randomized study is warranted to provide data for standardizing thrombolytic therapy in pediatric renal vein thrombosis.     

Occupational lead exposure and hearing loss

Studies of adults, children, and laboratory animals suggest an association between lead exposure and hearing loss. A causal relationship might direct mandated medical surveillance of lead-exposed workers to include audiometric testing. A cross-sectional, computerized dataset was obtained from a private occupational health screening company to examine the relationship between blood lead level and hearing loss. Audiometry and blood lead results were available for 183 workers. A statistically significant correlation was found between blood lead level and an elevated hearing threshold at 400 Hz (P = 0.03); no other frequencies showed such a correlation. This finding suggests either an interaction between nose exposure and lead, interaction of other exposure factors (such as cigarette smoking), or that factors other than biomechanical ones render the organ of Corti more susceptible at 4000 Hz. Further evaluation of these questions should be undertaken. Computerized databases created for worker surveillance may be a source for data useful for examining other causal connections in occupational settings.     

Short-pulse, eye-safe Nd:YAG laser using cavity-dumping

A short-pulse 1.444-μm laser based on Nd:YAG technology has been demonstrated. The 1.444-μm is eye-safe. With the cavity-dump technique, a pulse of 50 m× and 14 ns was obtained. The beam quality was excellent with an M² of 1.6 by the use of a telescopic resonator. Silicon-window polarizers were used to suppress the 1.06-μm radiation but showed 1.444-μm absorption as well     

Antimutagenic activity of casein against MNNG in the E. coli DNA repair host-mediated assay

The effect of caseinate and soy protein in the diet on the mutagenicity induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was assessed in-vivo and ex-vivo in the DNA-repair host-mediated assay and liquid suspension assay, respectively. Of the two proteins only casein showed a strong antimutagenic activity over the whole digestive tract, except in the stomach. It is suggested that the molecular structure of a protein determines its protective effect against mutagens: casein lacks secondary and tertiary structure so that amino acids are more readily available for interaction with the mutagen than with the amino acids in soy protein which is a globular protein.     

Major internal nuclear matrix proteins are common to different human cell types

Cancer invasion and metastasis are associated with matrix degradation. We describe a novel in vivo model of invasion by squamous epithelial neoplastic cells derived from transgenic mice grown on acellular human dermis. Human dermis was subjected to multiple freeze-thaw cycles to render it acellular, maintaining the basement membrane of the former dermal-epidermal junction. Cells representing discrete stages of a multistep transgenic mouse model of epidermal carcinogenesis (neonatal transgenic keratinocytes, moderately/poorly differentiated squamous cell carcinoma, and lymph node metastasis) were seeded onto the basement membrane surface, grown in culture for 4 days, grafted in a subpannicular pocket of athymic mice, and harvested after 3 weeks. Histological analysis demonstrated that neonatal transgenic keratinocytes did not degrade the basement membrane or invade the underlying dermis. In contrast, malignant cells derived from both a moderately differentiated squamous carcinoma and a lymph node metastasis were highly invasive. Immunohistochemical analysis revealed collagenase only in nests of invading malignant cells in contact with the dermal matrix, but not in the tumor mass remaining above the basement membrane, suggesting that this proteinase may be required for stromal invasion. This novel model recapitulates the events seen in malignant invasion: transgenic keratinocytes are unable to penetrate the dermis while cells from a moderately differentiated carcinoma and from lymph node metastasis consistently invade.